Achilles tendon ruptures result in significant pain, disability, and healthcare costs. Although both men and women show no difference in mean age or activity in sport at the time of rupture, gender disparity is prevalent with 75% and 25% of ruptures occurring in men and women, respectively. Differences in hormone physiology between sexes may be a factor influencing tendon health. These gender specific mechanisms may be protective of injury in women and could encourage more targeted rehabilitation. Unfortunately, current rehabilitation and treatment protocols are not gender specific. This is of particular importance since the current standard of care for male and female injuries rests on the assumption that Achilles tendons for otherwise healthy individuals should be treated synonymously. The overall goal of this competitive revision is to define the tissue-level properties of healing Achilles tendon, in a dose-dependent estrogen response. This will be completed in a set of clinically-relevant treatment paradigms to establish the mechanical mechanisms of successful, and potentially differential, tissue repair response between sexes. We propose that the healing tendon environment is governed by specific structural and biologic properties that are influenced by hormonal mechanisms. These hormonal mechanisms may optimize tendon loading to promote improved fatigue mechanical parameters, which in turn, govern successful rehabilitation progression. In addition, hormone levels may reduce the maximum stress generation of muscles and therefore the risk of tendon elongation, which has been correlated with poor clinical outcomes. We will determine Achilles tendon properties in both genders, as well as functional performance and passive joint mechanics following tendon injury in an animal model. Importantly, muscle will be evaluated as well. An animal model will be used to control the injury and treatment strategies, analyze tissue properties, and, through methods developed for the parent grant, determine clinically relevant measures that define tissue healing. Our overall hypothesis is that Achilles tendons from females are capable of accelerated rehabilitation and quicker return to activity due to decreased gastrocnemius and soleus muscle strength potential. The following specific aims are designed to directly challenge the absence of gender specific rehabilitation programs for Achilles tendon injuries. Aim 1: To determine whether uninjured control Achilles tendons and muscle in OVX, female, or male rats have superior mechanical, structural and biological properties. Aim 2: To determine whether repaired Achilles tendons and musculature in male, female, or OVX rats have superior mechanical, structural, and histological properties in a set of clinically relevant conditions. Thi study has high impact by increasing sex differences research in understanding the mechanisms of Achilles tendon injury risk and healing. This approach to study tissue level properties post-surgery as a function of estrogen levels may indicate that women could have accelerated rehabilitation protocols. Such findings could reduce high healthcare burdens due to excessive lost work days.